Muscle Spindle Afferent Activity Research Articles

Effect of Sympathetic Neurotransmitters on Muscle Spindle Afferent Sensitivity to Muscle Stretch in Adult Mice

The primary sensory input for proprioception, or the sense of body position in space, comes from muscle spindle afferents, which are mechanoreceptors that relay information about changes in muscle length. The muscle spindle is also innervated by sympathetic neurons, but the role of this sympathetic innervation on muscle spindle function is not well understood. Here we test the hypothesis that muscle spindle afferents will exhibit decreased firing in response to muscle stretch following exposure to the sympathetic neurotransmitters norepinephrine and epinephrine. To test this hypothesis we used an ex vivo mouse muscle‐nerve preparation. We recorded muscle spindle afferent firing activity during ramp‐and‐hold stretch and sinusoidal vibration before and after the addition of norepinephrine, epinephrine, or adrenergic receptor agonists. We observed significantly decreased firing during the end of stretch after both norepinephrine (100 µm, n=6) and epinephrine (30 µm, n=6). To identify the adrenergic receptor(s) involved, we also tested two ɑ2 adrenergic receptor agonists, Clonidine and Dexmedetomidine, and the ɑ1 receptor agonist phenylephrine. Both ɑ2 receptor agonists caused a decrease in muscle spindle afferent firing (1 mM clonidine, n=8 decreased firing; 100 µm dexmedetomidine, n=3). Phenylephrine had no significant effect on muscle spindle afferent firing (100 µm n=2; 30 µm n=6). These results show direct effects of sympathetic neurotransmitters on muscle spindle afferent stretch sensitivity and further support the hypothesis that sympathetic innervation of the muscle spindle plays an important role in modulating muscle spindle afferent activity and therefore motor control. Future studies will investigate the location of the adrenergic receptor(s) mediating this effect as well as the mechanism of action.

Development of an Optogenetic Method to Stimulate Gamma Motor Neurons In Vitro

The muscle spindle is a sensory organ located in the skeletal muscle that is critical for motor control and proprioception. The muscle spindle is innervated by stretch sensitive muscle spindle afferents and gamma motor neurons that control the length of the intrafusal muscle fibers and therefore the sensitivity of the stretch sensitive afferents. However, it has been challenging to study the gamma motor neurons since it is hard to specifically stimulate the gamma but not the alpha motor neurons that control the force generating extrafusal fibers. A previous study showed that alpha motor neurons were recruited from small diameter to large diameter with increasing optical intensities in mice expressing the blue light gated Channelrhodopsin2 (ChR2) in motor neurons (Llewellyn, et al., 2010). This is the reverse recruitment pattern of electrical stimulation. We hypothesized that gamma motor neurons, which are smaller than even the smallest alpha motor neurons, will be recruited first using low optical stimuli. The extensor digitorum longus muscle and sciatic nerve were dissected and placed in a tissue bath with oxygenated synthetic interstitial fluid. The sciatic nerve was attached to an extracellular suction electrode that recorded muscle spindle afferent activity. We used a light guide to deliver blue LED light (470nm; 0.5mW-5 mW) to the end of the nerve. We found that at lower levels of optical stimulation we recruited the gamma motor neurons as evidenced by an increased muscle spindle afferent firing rate and a pause after stimulation, which is typically observed following the release of stretch. Higher optical intensities were required to recruit alpha motor neurons to produce a twitch muscle contraction. Higher frequencies of optical stimulation led to greater increases in muscle spindle afferent firing rates as expected. We are currently testing additional stimulation frequencies and increasing our sample size to understand individual variability. We are also verifying that ChR2 is found in motor neurons only using immunohistochemistry. We will use this technique to study gamma motor neuron function and to produce a more physiological relevant system to study muscle spindle afferents. We can also use this method to screen for intrafusal fiber dysfunction in disease models.

The Role of Glutamate in Maintaining Muscle Spindle Afferent Excitability in Adult Mice

Group Ia and II muscle spindle afferents are sensory neurons critical to detecting muscle movement and length, which is important in proprioception and motor control. Glutamate is released by synaptic‐like vesicles (SLVs) at muscle spindle afferent nerve endings and exogenous glutamate increases sensory neuron firing rate during stretch (Bewick, et al., 2005). However, the activity of individual muscle spindle afferents was not measured, allowing for the possibility that this increased firing also included other sensory neurons known to have glutamate receptors, like nociceptors. Here we test the hypothesis that glutamate increases the firing rate of individual muscle spindle afferents. We isolated the extensor digitorum longus muscle and the sciatic nerve from adult mice (8–12 wks old) and recorded the activity of individual muscle spindle afferents during exogenous glutamate treatment. The muscle‐nerve preparation was perfused in an oxygenated synthetic interstitial fluid tissue bath, an extracellular recording electrode was placed on the nerve to measure the activity of individual muscle spindle afferents, and a battery of 4s ramp‐and‐hold stretches were performed on the muscle. Glutamate addition led to a significant increase in muscle spindle afferent firing rate during stretch (1mM; n=12, 18.8%). We also decreased glutamate release by blocking the vesicular glutamate transporter 1 (VGLUT1) with the inhibitor xanthurenic acid (XA). We found a significant decrease in muscle spindle afferent firing rates (3mM; n=17, −39%), with 5 afferents exhibiting a complete absence of firing. However, we noticed heterogeneity in muscle spindle afferent responses to glutamate and XA treatment, with some afferents not responding at all to the drug treatments. To confirm our pharmacological findings, we obtained a transgenic mouse line lacking a single copy of vesicular glutamate transporter 1 (VGLUT1; B6.129X1‐Sic17a7tm1Edw/MmcD; Fremeau, 2004). We observed two muscle spindle afferents responding normally to stretch, while another two failed to sustain firing at the end of stretch, something that is only rarely seen in wild type animals. This heterogeneity may be due to differences in VGLUT1 protein levels in individual afferents. We are currently increasing our sample size, but our preliminary results support our hypothesis that glutamate is critical to maintaining muscle spindle afferent firing during maintained stretch. These studies will lead to a better understanding of how muscle spindle afferent stretch sensitivity is regulated.Support or Funding InformationThis work was supported by NIH SC3 GM127195 (KAW) and NIH R25 GM071381 (SO and NV).

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Comparison between changes in secondary muscle spindle afferent activity and detrusor pressure (measured before the surgery; for the implantation of a sacral anterior root stimulator). Paraplegic 9. A. Activity changes of the afferent fiber SP2(1) following bladder catheter pulling (Figure 37Ba). Approx. mean activity level is represented by a dashed line at 7.5 IIs/0.8s ((APs -1)/0.8s). The activity above the mean is cross-hatched and is proposed to be due to parasympathetic activation. Root vS4. B. Detrusor pressure (pressure difference) changes taken from ‘C’. Note that changes in the detrusor pressure show almost exactly the same time course as do the activated changes of the secondary muscle spindle afferent fiber SP2(1) of ‘A’. Corresponding peaks are correlated by arrows. C. Abdominal pressure (measured as rectal pressure), intravesical pressure (urinary bladder pressure) and detrusor pressure (pressure difference) during retrograde filling before the surgery. One transient detrusor pressure increase, marked ‘B’, is used, after enlargement in ‘B’, to compare with the spindle afferent activity.

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Direct comparison of secondary muscle spindle afferent activity and motoneuron activity between the brain-dead human HT6 with a synergy of the bladder (A) and the paraplegic 9 with a dyssynergia of the bladder (B). A. Simultaneous measurements of activities of secondary muscle spindle afferents (a), parasympathetic preganglionic motoneurons (b) and oscillatory firing (high activity mode) of a sphincter motoneuron innervating the striated anal sphincter (c). Note that with the transient activity increase of the parasympathetic fibers (b) the secondary muscle spindle afferent fiber increased strongly its activity (a) for minutes, and the oscillatory firing sphincter motoneuron discontinued its oscillation (c) to reduce strongly its activity. bladder 3x = 3 times bladder catheter pulling. T ext. anal sphincter mot. = oscillation period of the sphincter α2-motoneuron innervating the anal sphincter. For further details, see Chapter V of [1].

The relationship between the sensory responses to ankle-joint loading and corticomotor excitability

ABSTRACTPurpose: Maintaining joint stability is dependent on the ability of the nervous system to sense and react to potentially injurious loads. In attempts to understand the neurophysiologic mechanisms underlying joint stability, this afferent and efferent activity has been quantified separately at the cortical, segmental and peripheral levels using various electrophysiologic techniques in vivo. However, no studies have attempted to quantify sensory and motor activation at multiple levels of the nervous system in a single subset, to understand potential adaptations for optimizing joint stability.Materials and Methods: Muscle spindle afferent activity and sensory cortex event-related desynchronization were quantified during ankle-joint loading; and motor excitability was assessed through transcranial magnetic stimulation and the Hoffmann reflex in a subset of 42 able-bodied individuals. Microneurography and electroencephalography were used to collect the muscle spindle afferent and sensory cortex activation, respectively, as joint load was applied using an ankle arthrometer. Separately, motor-evoked potentials were obtained from the tibialis anterior (TA) and soleus (SOL) using transcranial magnetic stimulation over the motor cortex, and compared to the reflexive responses evoked via sciatic nerve electrical stimulation.Results: Correlation coefficients revealed significant correlations between the motor threshold of the soleus and early muscle spindle afferent activity (r = −0.494) and early cortical event-related desynchronization (r = 0.470), as well as tibialis anterior motor-evoked potential size and late muscle spindle afferent activity (r = 0.499).Conclusions: The results of this study highlight the nervous system's capability to offset motor output based on the volume of sensory input at the segmental and cortical levels.

Muscle spindle and fusimotor activity in locomotion.

Mammals may exhibit different forms of locomotion even within a species. A particular form of locomotion (e.g. walk, run, bound) appears to be selected by supraspinal commands, but the precise pattern, i.e. phasing of limbs and muscles, is generated within the spinal cord by so-called central pattern generators. Peripheral sense organs, particularly the muscle spindle, play a crucial role in modulating the central pattern generator output. In turn, the feedback from muscle spindles is itself modulated by static and dynamic fusimotor (gamma) neurons. The activity of muscle spindle afferents and fusimotor neurons during locomotion in the cat is reviewed here. There is evidence for some alpha-gamma co-activation during locomotion involving static gamma motoneurons. However, both static and dynamic gamma motoneurons show patterns of modulation that are distinct from alpha motoneuron activity. It has been proposed that static gamma activity may drive muscle spindle secondary endings to signal the intended movement to the central nervous system. Dynamic gamma motoneuron drive appears to prime muscle spindle primary endings to signal transitions in phase of the locomotor cycle. These findings come largely from reduced animal preparations (decerebrate) and require confirmation in freely moving intact animals.

Distinguishing intrinsic from extrinsic factors underlying firing rate saturation in human motor units.

During voluntary contraction, firing rates of individual motor units (MUs) increase modestly over a narrow force range beyond which little additional increase in firing rate is seen. Such saturation of MU discharge may be a consequence of extrinsic factors that limit net synaptic excitation acting on motor neurons (MNs) or may be due to intrinsic properties of the MNs. Two sets of experiments involving recording of human biceps brachii MUs were carried out to evaluate saturation. In the first set, the extent of saturation was quantified for 136 low-threshold MUs during isometric ramp contractions. Firing rate-force data were best fit by a saturating function for 90% of MUs recorded with a maximum rate of 14.8 ± 2.0 impulses/s. In the second set of experiments, to distinguish extrinsic from intrinsic factors underlying saturation, we artificially augmented descending excitatory drive to biceps MNs by activation of muscle spindle afferents through tendon vibration. We examined the change in firing rate caused by tendon vibration in 96 MUs that were voluntarily activated at rates below and at saturation. Vibration had little effect on the discharge of MUs that were firing at saturation frequencies but strongly increased firing rates of the same units when active at lower frequencies. These results indicate that saturation is likely caused by intrinsic mechanisms that prevent further increases in firing rate in the presence of increasing synaptic excitation. Possible intrinsic cellular mechanisms that limit firing rates of motor units during voluntary effort are discussed.

The effect of tendon vibration on motor unit activity, intermuscular coherence and force steadiness in the elbow flexors of males and females.

Compartmentalized responses in motor unit (MU) activity of the short head (SH) and long head (LH) of the biceps brachii are observed following forearm position change. Differential muscle spindle afferent distribution has been proposed as a potential mechanism underlying this behaviour. Tendon vibration is an effective, non-invasive method of increasing muscle spindle afferent activity of a target muscle group offering a paradigm in which this hypothesis may be investigated further. To determine the effect of tendon vibration on MU recruitment and discharge rates of the SH and LH, muscle activity of the elbow flexors and triceps brachii, intermuscular coherence among the SH, LH, brachioradialis and triceps brachii and force steadiness in young males and females during isometric elbow flexion. Intramuscular electromyography (EMG) of the SH and LH, and surface EMG of the elbow flexors were recorded pre- and post-vibration during low-force isometric contractions. Motor unit recruitment thresholds, MU discharge rates and MU discharge variability; surface EMG amplitude, intermuscular coherence and force steadiness were determined pre- and post-vibration. Differential changes in all MU properties, EMG amplitude and intermuscular coherence were observed among elbow flexors. Although MU properties exhibited differential changes, they accounted for little variance in isometric force steadiness. However, intermuscular EMG coherence among all muscles investigated was reduced post-vibration. Uncoupling of common oscillatory input as a result of differential muscle spindle afferent inputs to elbow flexors may be responsible for the reduction in force steadiness following tendon vibration and a forearm position change.

Cardiorespiratory coupling of sympathetic outflow in humans: a comparison of respiratory and cardiac modulation of sympathetic nerve activity to skin and muscle

What is the central question of this study?Muscle sympathetic nerve activity (MSNA) is well known to be modulated by the arterial baroreceptors and respiration, but what are the magnitudes of cardiac and respiratory modulation of skin sympathetic nerve activity (SSNA), which primarily subserves thermoregulation?What is the main finding and what is its importance?Using direct microelectrode recordings of MSNA and SSNA in awake humans, we show that the magnitude of respiratory modulation of SSNA is identical to that of MSNA, the primary difference between the two sources of sympathetic outflow being the greater cardiac modulation of MSNA. This emphasises the role of the baroreceptors in entraining sympathetic outflow to muscle. It is well known that microelectrode recordings of skin sympathetic nerve activity (SSNA) in awake human subjects reveal spontaneous bursts of activity with no overt modulation by changes in blood pressure or respiration, in contrast to the clear cardiac and respiratory modulation of muscle sympathetic nerve activity (MSNA). However, cross-correlation analysis has revealed that, like individual muscle vasoconstrictor neurones, the firing of individual cutaneous vasoconstrictor neurones is temporally coupled to both the cardiac and respiratory rhythms during cold-induced cutaneous vasoconstriction, and the same is true of single sudomotor neurones during heat-induced sweating. Here, we used cross-correlation analysis to determine whether SSNA exhibits cardiac and respiratory modulation in thermoneutral conditions and to compare respiratory and cardiac modulation of SSNA with that of MSNA. Oligounitary recordings of spontaneous SSNA (n = 20) and MSNA (n = 18) were obtained during quiet, unrestrained breathing. Respiration was recorded by a strain-gauge transducer around the chest and ECG recorded by surface electrodes. Respiratory and cardiac modulation of SSNA and MSNA were quantified by fitting polynomial equations to the cross-correlation histograms constructed between the sympathetic spikes and respiration or ECG. The amplitude of the respiratory modulation (52.5 ± 3.4%) of SSNA was not significantly different from the amplitude of the cardiac modulation (46.6 ± 3.2%). Both were comparable to the respiratory modulation of MSNA (47.7 ± 4.2%), while cardiac modulation of MSNA was significantly higher (89.8 ± 1.5%). We conclude that SSNA and MSNA share similar levels of respiratory modulation, the primary difference between the two sources of sympathetic outflow being the marked cardiac modulation of MSNA provided by the baroreceptors.

Modulation of human motoneuron activity by a mental arithmetic task

This study aimed to determine whether the performance of a mental task affects motoneuron activity. To this end, the tonic discharge pattern of wrist extensor motor units was analyzed in healthy subjects while they were required to maintain a steady wrist extension force and to concurrently perform a mental arithmetic (MA) task. A shortening of the mean inter-spike interval (ISI) and a decrease in ISI variability occurred when MA task was superimposed to the motor task. Aloud and silent MA affected equally the rate and variability of motoneuron discharge. Increases in surface EMG activity and force level were consistent with the modulation of the motor unit discharge rate. Trial-by-trial analysis of the characteristics of motor unit firing revealed that performing MA increases activation of wrist extensor SMU. It is suggested that increase in muscle spindle afferent activity, resulting from fusimotor drive activation by MA, may have contributed to the increase in synaptic inputs to motoneurons during the mental task performance, likely together with enhancement in the descending drive. The finding that a mental task affects motoneuron activity could have consequences in assessment of motor disabilities and in rehabilitation in motor pathologies.

Characterization of adult mouse muscle spindle afferents in an in vitro isolated muscle nerve preparation

Changes in muscle spindle afferent activity has been demonstrated in models of muscle pain and diabetes and may also be altered in Restless Legs Syndrome. Here we describe a novel in vitro adult mouse muscle nerve preparation ideally suited to measure plasticity in muscle afferent activity. Briefly, we removed the Extensor Digitorum Longus (EDL) and its nerve from adult (2-month old) male C57Bl/6 mice. The isolated muscle was attached to a force and length controller (Aurora). The length at which the highest force following twitch contraction occurred was set as the resting length (Lo). Muscle afferent activity was recorded using a suction electrode and individual units discriminated using WaveClus (Quiroga, 2004). A battery of stretches and vibrations were performed at Lo, Lo+ 5%, and Lo-5%. We collected the responses of at least 2 stretch sensitive units in 12 muscles at room temperature. Group Ia afferents were found to have clear dynamic sensitivity and showed entrainment to vibration with amplitudes as low 5 μM. Muscles were stretched 2.5%, 5%, and 7.5% Lo and increased firing frequency by a constant number of impulses per mm stretch, similar to that reported in vivo for rats and cats. Health of the preparation was confirmed following stretch in a subset of animals by determining the maximal isometric tension (23.4 ± 2.5 N/cm2, n = 6). This research was supported by K12 GM000680 NIH/NIGMS More Division (KAW) and Pfizer (SH).

Spike sorting of muscle spindle afferent nerve activity recorded with thin-film intrafascicular electrodes.

Afferent muscle spindle activity in response to passive muscle stretch was recorded in vivo using thin-film longitudinal intrafascicular electrodes. A neural spike detection and classification scheme was developed for the purpose of separating activity of primary and secondary muscle spindle afferents. The algorithm is based on the multiscale continuous wavelet transform using complex wavelets. The detection scheme outperforms the commonly used threshold detection, especially with recordings having low signal-to-noise ratio. Results of classification of units indicate that the developed classifier is able to isolate activity having linear relationship with muscle length, which is a step towards online model-based estimation of muscle length that can be used in a closed-loop functional electrical stimulation system with natural sensory feedback.

Signal Processing for Neural Spike Trains

Signal Processing for Neural Spike Trains

The functional role of different neural activation profiles during precision grip: An artificial neural network approach

A dynamic and recurrent artificial neural network was used to investigate the functional properties of firing patterns observed in the primary motor (M1) and the primary somatosensory (S1) cortex of the behaving monkey during control of precision grip force. In the behaving monkey it was found that neurons in M1 and in S1 increase their firing activity with increasing grip force, as do the intrinsic and extrinsic hand muscles implicated in the task. However, some neurons also decreased their activity as a function of increasing force. The functional implication of these latter neurons is not clear and has not been elucidated so far. In order to explore their functional implication, we therefore simulated patterns of neural activity in artificial neural networks that represent cortical, spinal and afferent neural populations and tested whether particular activity profiles would emerge as a function of the input and of the connectivity of these networks. The functional implication of units with emergent or imposed decreasing activity was then explored. Decreasing patterns of activity in M1 units did not emerge from the networks. However, the same networks generated decreasing activity if imposed as target patterns. As indicated by the emerging weight space, M1 projection units with decreasing patterns are functionally less involved in driving alpha motoneurons than units with increasing profiles. Furthermore, these units did not provide significant fusimotor drive, whereas those with increasing profiles did. Fusimotor drive was a function of the (imposed) form of muscle spindle afferent activity: with gamma (fusimotor) drive, muscle spindle afferents provided signals other than muscle length (as observed experimentally). The network solutions thus predict a functional dichotomy between increasing and decreasing M1 neurons: the former primarily drive alpha and gamma motoneurons, the latter only weakly alpha motoneurons.

Responses of muscle spindles in feline dorsal neck muscles to electrical stimulation of the cervical sympathetic nerve

Previous studies performed in jaw muscles of rabbits and rats have demonstrated that sympathetic outflow may affect the activity of muscle spindle afferents (MSAs). The resulting impairment of MSA information has been suggested to be involved in the genesis and spread of chronic muscle pain. The present study was designed to investigate sympathetic influences on muscle spindles in feline trapezius and splenius muscles (TrSp), as these muscles are commonly affected by chronic pain in humans. Experiments were carried out in cats anesthetized with alpha-chloralose. The effect of electrical stimulation (10 Hz for 90 s or 3 Hz for 5 min) of the peripheral stump of the cervical sympathetic nerve (CSN) was investigated on the discharge of TrSp MSAs (units classified as Ia-like and II-like) and on their responses to sinusoidal stretching of these muscles. In some of the experiments, the local microcirculation of the muscles was monitored by laser Doppler flowmetry. In total, 46 MSAs were recorded. Stimulation of the CSN at 10 Hz powerfully depressed the mean discharge rate of the majority of the tested MSAs (73%) and also affected the sensitivity of MSAs to sinusoidal changes of muscle length, which were evaluated in terms of amplitude and phase of the sinusoidal fitting of unitary activity. The amplitude was significantly reduced in Ia-like units and variably affected in II-like units, while in general the phase was affected little and not changed significantly in either group. The discharge of a smaller percentage of tested units was also modulated by 3-Hz CSN stimulation. Blockade of the neuromuscular junctions by pancuronium did not induce any changes in MSA responses to CSN stimulation, showing that these responses were not secondary to changes in extrafusal or fusimotor activity. Further data showed that the sympathetically induced modulation of MSA discharge was not secondary to the concomitant reduction of muscle blood flow induced by the stimulation. Hence, changes in sympathetic outflow can modulate the afferent signals from muscle spindles through an action exerted directly on the spindles, independent of changes in blood flow. It is suggested that such an action may be one of the mechanisms mediating the onset of chronic muscle pain in these muscles in humans.

Effects in feline gastrocnemius-soleus motoneurones induced by muscle fatigue

Responses of gastrocnemius-soleus (G-S) motoneurones to stretches of the homonymous muscles were recorded intracellularly in decerebrate cats before, during and after fatiguing stimulation (FST) of G-S muscles. Ventral roots (VR) L7 and S1 were cut, and FST was applied to VR S1, a single FST session including 4 to 5 repetitions of 12-s periods of regular 40 s(-1) stimulation. Muscle stretches consisted of several phases of slow sinusoidal shortening-lengthening cycles and intermediate constant lengths. The maximal stretch of the muscles was 8.8 mm above the rest length. Effects of FST on excitatory postsynaptic potentials (EPSPs) and spikes evoked by the muscle stretches were studied in 12 motoneurones from ten experiments. Stretch-evoked EPSPs and firing were predominantly suppressed after FST, with the exception of a post-contraction increase of the first EPSP after FST, which was most likely due to after-effects in the activity of muscle spindle afferents. The post-fatigue suppression of EPSPs and spike activity was followed by restoration within 60-100 s. Additional bouts of FST augmented the intensity of post-fatigue suppression of EPSPs, with the spike activity sometimes disappearing completely. FST itself elicited EPSPs at latencies suggesting activation of muscle spindle group Ia afferents via stimulation of beta-fibres. The suppression of the stretch-evoked responses most likely resulted from fatigue-evoked activity of group III and IV muscle afferents. Presynaptic inhibition could be one of the mechanisms involved, but homosynaptic depression in the FST-activated group Ia afferents may also have contributed.

Human pain models: other: Effects of experimental muscle pain on the sensitivity of primary muscle spindle afferents in human: A microneurographic study

An experimental model based on i.m. injections of hypertonic saline (HS) has been extensively used when investigating the effects of muscle pain on motor control in both animal and human studies. Clearly, HS induced muscle pain influences several aspects of motor control. It has been suggested that some of these effects are caused by changes in the activity of the fusimotor-muscle spindle system. Data from our lab have shown that i.m injections of HS in cat do indeed influence the fusimotor-muscle spindle system. However, no studies have yet investigated the direct effects of HS injections on the fusimotor-muscle spindle system in human subjects. This paper will present preliminary data from a human model and compare these with previous data from a cat model. In the human model, primary muscle spindle afferent (MSA) activity from the ankle muscles was recorded from the peroneal nerve in human subjects using the microneurography technique. The sensitivity of the afferents to sinusoidal stretching was assessed after injections of 0,5 ml isotonic or hypertonic saline into the Tibialis Anterior muscle via an infusion catheter. In the cat model, responses of two to nine MSAs from the gastrocnemius muscles were recorded simultaneously from the dorsal root. These afferents were tested in a way similar to that used in the human model, with i.m. injections of either hypertonic saline or Tyrodes solution (control). In both studies, MSA sensitivity was assessed by calculating the mean rate of discharge and the depth of modulation of the afferent responses to sinusoidal stretching. When comparing the results form the two experimental models, it seems as if the strong influence of muscle pain on the fusimotor-muscle spindle system seen in cat is also present in man.

Inhibition of muscle spindle afferent activity during masseter muscle fatigue in the rat.

The influence of muscle fatigue on the jaw-closing muscle spindle activity has been investigated by analyzing: (1) the field potentials evoked in the trigeminal motor nucleus (Vmot) by trigeminal mesencephalic nucleus (Vmes) stimulation, (2) the orthodromic and antidromic responses evoked in the Vmes by stimulation of the peripheral and central axons of the muscle proprioceptive afferents, and (3) the extracellular unitary discharge of masseter muscle spindles recorded in the Vmes. The masseter muscle was fatigued by prolonged tetanic masseter nerve electrical stimulation. Pre- and postsynaptic components of the potentials evoked in the Vmot showed a significant reduction in amplitude following muscle fatigue. Orthodromic and antidromic potentials recorded in the Vmes also showed a similar amplitude decrease. Furthermore, muscle fatigue caused a decrease of the discharge frequency of masseter muscle spindle afferents in most of the examined units. The inhibition of the potential amplitude and discharge frequency was strictly correlated with the extent of muscle fatigue and was mediated by the group III and IV afferent muscle fibers activated by fatigue. In fact, the inhibitory effect was abolished by capsaicin injection in the masseter muscle that provokes selective degeneration of small afferent muscle fibers containing neurokinins. We concluded that fatigue signals originating from the muscle and traveling through capsaicin-sensitive fibers are able to diminish the proprioceptive input by a central presynaptic influence. In the second part of the study, we examined the central projection of the masseter small afferents sensitive to capsaicin at the electron-microscopic level. Fiber degeneration was induced by injecting capsaicin into the masseter muscle. Degenerating terminals were found on the soma and stem process in Vmes and on the dendritic tree of neurons in Vmot. This suggests that small muscle afferents may influence the muscle spindle activity through direct synapses on somata in Vmes and on dendrites of neurons in Vmot.

DISTURBED PROPRIOCEPTION FOLLOWING COMPUTER MOUSE USE

Changes in proprioception (movement and position perception), facilitated by alterations in muscle spindle afferent activity, arise following repetitive muscle activity, especially if fatigue ensues. Consequently, a hypothesis was put forth that work-related musculoskeletal disorders (both in the genesis and spread of muscle pain) might be attributed to diminished proprioceptive function. PURPOSE: To determine the effect of computer mouse use on proprioception. METHODS: Position sense acuity of the wrist joint for 23 normal volunteers (11 females and 12 males) was determined before and after a laboratory model of repetitive mouse use entailing painting small squares on the computer screen uninterrupted for 45 minutes. Wrist position sense was determined by noting the angular error for subjects actively reproducing a series of 15 test trials randomly displaced between 0○ and 30○ of flexion, while starting at 30○ of extension. The variability of error (VE) (i.e. standard deviation of the 15 trials) was computed as the assessment variable of accuracy. In addition, subjective fatigue was assessed using the Borg scale before, after and for each 5 min-interval during the painting protocol. RESULTS: A 2-way ANOVA revealed an increase in VE following mouse use for the group (p < 0.05), but no difference between gender was detected. Fatigue ratings increased throughout the painting protocol for the group (p < 0.001); furthermore a significant interaction was found between gender (p < 0.05), which displayed as males exhibiting a steep increase in the first 10 minutes followed by a plateau, while for females a constant linear increase was observed throughout. CONCLUSIONS: Since optimal motor control is largely dependent on proprioception, it may be implied that extended mouse use could lead to increased workload, thereby increasing intramuscular metabolites and/or inflammatory substances which would further impact proprioception (i.e. an unfavorable cycle of events). Thus, the current findings may provide insight into the poorly understood mechanism behind computer related musculoskeletal disorders. Supported in part by the Swedish Council for Work Life Research, and technically by Monica Edstrom and Majken Rahm.